Contractile effects of cardiac neuropeptides in isolated canine atrial and ventricular muscles

1989 ◽  
Vol 257 (4) ◽  
pp. H1082-H1087 ◽  
Author(s):  
D. F. Rigel ◽  
I. L. Grupp ◽  
A. Balasubramaniam ◽  
G. Grupp
Keyword(s):  
Isometric Force ◽  
Contractile Force ◽  
Adrenergic Blockade ◽  
Canine Heart ◽  
Inotropic Action ◽  
Inotropic Effects ◽  
Calcitonin Gene ◽  
Positive Inotropic Effects ◽  
The Right ◽  
Ventricular Trabeculae

Contractile effects of the cardiac neuropeptides vasoactive intestinal polypeptide (VIP), peptide histidine isoleucine (PHI), neuropeptide Y (NPY), calcitonin gene-related peptide (CGRP), and neurotensin (NT) were compared with those of l-isoproterenol (ISO) in isolated canine atrial and ventricular trabeculae muscles stimulated to contract at 1 Hz. In ventricular muscles, ISO, VIP, and PHI augmented developed isometric force by approximately 100%. VIP and PHI were three times and 1/10, respectively, as potent as ISO. VIP also exhibited positive inotropic effects in atrial trabeculae. The contractile responses to VIP were unchanged after beta-adrenergic blockade with nadolol at a concentration (10 microM) that shifted the ISO dose-response curve two to three orders of magnitude to the right. In atrial and ventricular trabeculae, NPY (1 microM) attenuated contractile force by 36 +/- 8 and 30 +/- 4%, respectively. Each peptide also caused comparable increases or decreases in the rate of development of force and the rate of relaxation. CGRP and NT caused no significant changes in developed force in either atrial or ventricular muscles in concentrations up to 1 microM. Our results indicate a potential positive inotropic action of endogenous VIP and PHI and a cardiodepressant effect of endogenous NPY in the canine heart.

Vasoactive intestinal peptide has a direct positive inotropic effect on isolated human myocardial trabeculae

2001 ◽  
Vol 101 (6) ◽  
pp. 637-643 ◽  
Author(s):  
Ole SAETRUM OPGAARD ◽  
Mikael KNUTSSON ◽  
René DE VRIES ◽  
Beril TOM ◽  
Pramod R. SAXENA ◽  
...  
Keyword(s):  
Left Ventricle ◽  
Vasoactive Intestinal Peptide ◽  
Right Atrium ◽  
Human Heart ◽  
Positive Inotropic Effect ◽  
Contractile Force ◽  
Inotropic Effect ◽  
Inotropic Effects ◽  
The Right ◽  
Ventricular Trabeculae

The aim of the present study was to assess the inotropic effects of vasoactive intestinal peptide (VIP) on isolated myocardial trabeculae from the right atrium and the left ventricle of human hearts. Furthermore, using reverse transcriptase-PCR, we wanted to determine the presence of mRNAs encoding the three cloned human VIP receptors, VPAC1, VPAC2 and PAC1. The trabeculae were paced at 1.0Hz in tissue baths, and changes in isometric contractile force upon exposure to agonist were studied. VIP had a potent positive inotropic effect in some of the atrial and ventricular trabeculae tested. This effect was almost completely blocked by the VIP-receptor antagonist VIP-(6-28). mRNAs encoding the human VPAC1, VPAC2 and PAC1 receptors were detected in human myocardial trabeculae from both the right atrium and the left ventricle. In conclusion, VIP has a direct positive inotropic effect in both the atria and the ventricles of the human heart. The presence of mRNAs for the VPAC1, VPAC2 and PAC1 receptors suggest that VIP may mediate its effect via these receptors.

Pyruvate potentiates inotropic effects of isoproterenol and Ca2+ in rabbit cardiac muscle preparations

2000 ◽  
Vol 279 (2) ◽  
pp. H702-H708 ◽  
Author(s):  
Hans-Peter Hermann ◽  
Oliver Zeitz ◽  
Boris Keweloh ◽  
Gerd Hasenfuss ◽  
Paul M. L. Janssen
Keyword(s):  
Energy Demand ◽  
Contractile Force ◽  
Potential Importance ◽  
Inotropic Response ◽  
Inotropic Effects ◽  
Individual Effects ◽  
Positive Inotropic Effects ◽  
Series Of Experiments ◽  
The Individual ◽  
Mere Addition

Catecholamines and elevated extracellular Ca2+concentration ([Ca2+]o) augment contractile force by increased Ca2+ influx and subsequent increased sarcoplasmic reticulum (SR) Ca2+ release. We tested the hypothesis that pyruvate potentiates Ca2+ release and inotropic response to isoproterenol and elevated [Ca2+]o, since this might be of potential importance in a clinical setting to circumvent deleterious effects on energy demand during application of catecholamines. Therefore, we investigated isometrically contracting myocardial preparations from rabbit hearts at 37°C, pH 7.4, and a stimulation frequency of 1 Hz. At a [Ca2+]o of 1.25 mM, pyruvate (10 mM) alone increased developed force (Fdev) from 1.89 ± 0.42 to 3.62 ± 0.62 (SE) mN/mm2 ( n = 8, P < 0.05) and isoproterenol (10−6 M) alone increased Fdev from 2.06 ± 0.55 to 25.11 ± 2.1 mN/mm2 ( P < 0.05), whereas the combination of isoproterenol and pyruvate increased Fdevoverproportionally from 1.89 ± 0.42 to 33.31 ± 3.18 mN/mm2 ( P < 0.05). In a separate series of experiments, we assessed SR Ca2+ content by means of rapid cooling contractures and observed that, despite no further increase in Fdev by increasing [Ca2+]o from 8 to 16 mM, 10 mM pyruvate could still increase Fdev from 26.4 ± 6.8 to 29.7 ± 7.1 mN/mm2( P < 0.05, n = 9) as well as the Ca2+ load of the SR. The results show that the positive inotropic effects of pyruvate potentiate the inotropic effects of isoproterenol or Ca2+, because in the presence of pyruvate, Ca2+ and isoproterenol induced larger increases in inotropy than can be calculated by mere addition of the individual effects.

Positive inotropic response to inosine in the in situ canine heart

1977 ◽  
Vol 233 (4) ◽  
pp. H438-H443 ◽  
Author(s):  
C. E. Jones ◽  
J. X. Thomas ◽  
M. D. Devous ◽  
C. P. Norris ◽  
E. E. Smith
Keyword(s):  
Heart Rate ◽  
Blood Flow ◽  
Arterial Pressure ◽  
Substantial Effect ◽  
Contractile Force ◽  
Left Ventricular ◽  
Canine Heart ◽  
Inotropic State ◽  
Arterial Blood ◽  
The Right

Effects of inosine on left ventricular contractile force, circumflex blood flow, heart rate, and arterial pressure were investigated in mongrel dogs. Infusion of 50 ml of 10, 25, or 50 mM inosine into the right atrium over 5 min produced arterial blood inosine concentrations of 20-120 microM. Infusion of inosine concentrations of 10 mM or greater produced statistically significant increases in contractile force and circumflex blood flow (P less than 0.05). The increases in contractile force and circumflex blood flow caused by 50 inosine were approximately 40% and 110%, respectively. No statistically significant increases in heart rate or arterial pressure were observed during infusion of inosine at any concentration. Administration of propranolol (2 mg/kg) in no way altered the effects of inosine on contractile force or circumflex blood flow. Thus, the present study suggests that inosine in concentrations which may be produced in the myocardium during stressful conditions causes a substantial effect on the inotropic state of the heart and that the effects of inosine are not mediated through adrenergic mechanisms.

Effects of Ions, Ouabain, Epinephrine, and Tetrodotoxin on Glucose Metabolism and on Contractility in the Perfused Guinea Pig Heart

1972 ◽  
Vol 50 (6) ◽  
pp. 584-593 ◽  
Author(s):  
E. Benmouyal
Keyword(s):  
Glucose Metabolism ◽  
Guinea Pig ◽  
Glucose Utilization ◽  
Contractile Force ◽  
Additive Effects ◽  
Guinea Pig Heart ◽  
Inotropic Effects ◽  
Antagonistic Effects ◽  
Positive Inotropic Effects ◽  
Opposite Action

In the perfused guinea pig heart, the rate of glucose-U-14C oxidation to 14CO2 was directly related to the external ratio [Ca2+]/[Na+]2. The metabolic stimulatory effects of ouabain were concentration-dependent, and those brought about by epinephrine were not prevented by the presence of ouabain or added Ca2+. The increased glucose utilization produced by ouabain or Ca2+ was reduced by tetrodotoxin (TTX), whereas that produced by epinephrine or reduced extracellular Na+ (100 mM) was not. It was also found that TTX inhibited the positive inotropic effects of Ca2+ and ouabain, but did not reduce the contractile force during perfusion in presence of epinephrine or at 100 mM Na+. It is concluded that (a) ouabain (or Ca2+) and epinephrine, producing additive effects, have different modes of action; (b) TTX and ouabain (or Ca2+) have antagonistic effects, probably resulting from their opposite action on calcium movements.

The effects of isoproterenol, UDCG 115, and caffeine on the heat related to excitation–contraction coupling in heart muscle

1987 ◽  
Vol 65 (4) ◽  
pp. 659-666 ◽  
Author(s):  
Edward M. Blanchard ◽  
Norman R. Alpert
Keyword(s):  
Negative Inotropic Effect ◽  
Mechanical Relaxation ◽  
Inotropic Effects ◽  
Inotropic Drugs ◽  
Positive Inotropic Effects ◽  
Diacetyl Monoxime ◽  
Butanedione Monoxime ◽  
The Right ◽  
Initial Heat ◽  
Independent Heat

A myothermal technique was used to measure initial heat and tension independent heat from isometrically contracting papillary muscles taken from the right ventricle of rabbits. Tension independent heat produced by the muscle at Lo was isolated with a 2,3-butanedione monoxime (diacetyl monoxime) – hyperosmotic Krebs solution. The effects of the inotropic drugs isoproterenol (1 × 10−7 M), UDCG 115 (2 × 10−4M), and caffeine (2 × 10−3 M) on heat and mechanical output were measured. We tested the hypothesis that these drugs alter peak twitch tension by increasing the total amount of Ca2+ cycled during the twitch, assuming that net tension independent heat is proportional to total Ca2+ cycled. The hypothesis was rejected for each drug as the positive inotropic effects of isoproterenol and UDCG 115 on twitch tension were not accompanied by increases in net tension independent heat. Net tension independent heat was actually depressed by UDCG 115. The negative inotropic effect of caffeine on twitch tension was accompanied by an increase in tension independent heat at times between the end of mechanical relaxation and the next stimulus. Possible mechanisms to account for these results are discussed.

scholarly journals Inotropic and lusitropic effects of calcitonin gene-related peptide in the heart

2013 ◽  
Vol 304 (11) ◽  
pp. H1525-H1537 ◽  
Author(s):  
Mustafa Al-Rubaiee ◽  
Pandu R. Gangula ◽  
Richard M. Millis ◽  
Robin K. Walker ◽  
Nsini A. Umoh ◽  
...  
Keyword(s):  
Vena Cava ◽  
Systolic Pressure ◽  
Calcitonin Gene Related Peptide ◽  
Left Ventricular ◽  
In Vivo Studies ◽  
Stroke Work ◽  
Inotropic Effects ◽  
Related Peptide ◽  
Calcitonin Gene ◽  
Positive Inotropic Effects

Previous studies have demonstrated positive-inotropic effects of calcitonin gene-related peptide (CGRP), but the mechanisms remain unclear. Therefore, two experiments were performed to determine the physiological correlates of the positive-inotropic effects of CGRP. Treatments designed to antagonize the effects of physiologically active CGRP1–37 included posttreatment with CGRP8–37 and pretreatment with LY-294002 (LY, an inhibitor of phosphatidylinositol 3-kinase), 17β-estradiol (E), and progesterone (P) were also used to modulate the effects of CGRP1–37. Experiment 1 was in vitro studies on sarcomeres and cells of isolated adult rat cardiac myocytes. CGRP1–37, alone and in combination with E and P, decreased sarcomere shortening velocities and increased shortening percentages, effects that were antagonized by CGRP8–37, but not by LY. CGRP1–37 increased resting intracellular calcium ion concentrations and Ca2+ influxes, effects that were also antagonized by both CGRP8–37 and LY. Experiment 2 was in vivo studies on left ventricular pressure-volume (PV) loops. CGRP1–37 increased end-systolic pressure, ejection fraction, and velocities of contraction and relaxation while decreasing stroke volume, cardiac output, stroke work, PV area, and compliance. After partial occlusion of the vena cava, CGRP1–37 increased the slope of the end-systolic PV relationship. CGRP8–37 and LY attenuated most of the CGRP-induced changes. These findings suggest that CGRP-induced positive-inotropic effects may be increased by treatments with estradiol and progesterone and inhibited by LY. The physiological correlates of CGRP-induced positive inotropy observed in rat sarcomeres, cells, and intact hearts are likely to reveal novel mechanisms of heart failure in humans.

scholarly journals Diabetes-associated Alterations in Volatile Anesthetic Actions on Contractile Response to Norepinephrine in Isolated Mesenteric Resistance Arteries

2010 ◽  
Vol 112 (3) ◽  
pp. 595-606 ◽  
Author(s):  
Jun Yoshino ◽  
Takashi Akata ◽  
Kazuhiro Shirozu ◽  
Kaoru Izumi ◽  
Sumio Hoka
Keyword(s):  
Response Curve ◽  
Contractile Response ◽  
Isometric Force ◽  
Volatile Anesthetic ◽  
Volatile Anesthetics ◽  
Mesenteric Arteries ◽  
Resistance Arteries ◽  
Calcitonin Gene ◽  
The Right ◽  
Concentration Response Curve

Background Clinical concentrations of volatile anesthetics significantly influence contractile response to the sympathetic neurotransmitter norepinephrine although its precise mechanisms remain unclarified. In this study, we investigated its possible alterations in diabetes, as well as its underlying mechanisms. Methods Isometric force was recorded in small mesenteric arteries from streptozotocin-induced diabetic and age-matched control rats. Results The concentration-response curve for acetylcholine-induced endothelium-dependent relaxation was shifted to the right in diabetic arteries compared with controls. The concentration-response curve for norepinephrine-induced contraction was shifted to the left and upward by both endothelial denudation and diabetic induction. In the presence of endothelium, isoflurane or sevoflurane enhanced norepinephrine-induced contraction in control arteries but not in diabetic arteries; however, in its absence, both anesthetics identically inhibited norepinephrine-induced contraction in both groups. In control arteries, the isoflurane- or sevoflurane-induced enhancement was not affected by adrenomedullin22-52, calcitonin gene-related peptide8-37, 18beta-glycyrrhetinic acid, N-nitro l-arginine, ouabain, Ba, indomethacin, losartan, ketanserin, BQ-123, and BQ-788. Conclusions In diabetes, vascular responses to acetylcholine, norepinephrine, and volatile anesthetics are altered in mesenteric resistance arteries, presumably reflecting endothelial dysfunction and possibly underlying circulatory instability during administration of either anesthetic. Some endothelial mechanisms that are impaired in diabetes would be involved in the anesthetic-induced enhancement of norepinephrine-induced contraction. However, the vasoregulatory mechanism mediated by adrenomedullin, calcitonin gene-related peptide, myoendothelial gap junction, nitric oxide, endothelium-derived hyperpolarizing factor, cyclooxygenase products, angiotensin II, serotonin, or endothelin-1, all of which have been suggested to be impaired in diabetes, would not be involved in the enhancement.

Characteristics of tetanic contractions in caffeine-treated rat myocardium

1995 ◽  
Vol 73 (5) ◽  
pp. 638-643 ◽  
Author(s):  
C. M. Leite ◽  
D. V. Vassallo ◽  
J. G. Mill
Keyword(s):  
Sarcoplasmic Reticulum ◽  
Contractile Response ◽  
Isometric Force ◽  
Muscle Length ◽  
Rat Myocardium ◽  
Inotropic Effects ◽  
Perfusion Chamber ◽  
Positive Inotropic Effects ◽  
Contractile Activation ◽  
Tetanic Tension

Skinned fiber preparations are used to obtain the maximal contractile activation of isolated myocardial preparations. Tetanic contractions elicited in the presence of sarcoplasmic reticulum inhibitors have also been used as an alternative method to produce maximal active tension in the intact myocardium. In this work our purpose was to define the best conditions to obtain tetanic contractions in the rat myocardium and to compare the influence of muscle length and inotropic interventions (Ca2+ and Bay K8644) in the tension produced in twitches and tetanic contractures. Papillary muscles were mounted in a perfusion chamber to record isometric force. Tetanic contractions were elicited by using suprathreshold stimulation with rectangular pulses (10 ms duration) at 5 Hz in the presence of 2.5 mM caffeine. Caffeine depressed the twitch tension but the tetanic tension was similar to that produced under steady-state stimulation (0.5 Hz) in control conditions. Tetanic and twitch tensions were similar along the whole extension of the length–tension curve and under the positive inotropic effects produced by Ca2+ (0.25 to 3.75 mM) or by the Ca2+-channel agonist Bay K8644 (1 μM). During long tetanic stimuli (60 s) a time-dependent tension decay was observed. This decay was prolonged by reducing the extracellular K+ from 5.4 to 1.0 mM, suggesting that Ca2+ extrusion through the Na–Ca exchanger seems to occur during tetanic stimulation. Since tetanic tension was never higher than the tension obtained in twitches elicited at the same Ca2+ concentration (0.5 Hz), we conclude that tetanic contractures represent a useful tool to investigate the contractile response of intact myocardial preparations with a nonfunctional sarcoplasmic reticulum. However, our results indicate that the maximal activation of the contractile machinery in the rat myocardium seems to be only achieved in twitches elicited in high extracellular Ca2+ concentrations and with a functional sarcoplasmic reticulum.Key words: cardiac muscle, excitation–contraction coupling, sarcoplasmic reticulum, tetanic contracture, Na–Ca exchange.

Association of the positive inotropic action of ouabain with a second species of digitalis receptors

1985 ◽  
Vol 63 (5) ◽  
pp. 476-486 ◽  
Author(s):  
Itsuo Kurobane ◽  
Dhirendra L. Nandi ◽  
George T. Okita
Keyword(s):  
Half Life ◽  
Inotropic Action ◽  
Ouabain Binding ◽  
Cardiac Sarcolemma ◽  
Inotropic Effects ◽  
Positive Inotropic Action ◽  
Positive Inotropic Effects ◽  
Life Values ◽  
Slow Dissociation

Studies were conducted to determine whether Na–K ATPase or a second species of digitalis receptors in canine cardiac sarcolemma membrane preparations is associated with the positive inotropic action of nontoxic concentrations of ouabain. [3H]ouabain association and dissociation experiments using highly enriched sarcolemma preparations from canine ventricle indicate the presence of two species of ouabain binding receptors. Ouabain binding to Na–K ATPase of the sarcolemma preparation requires supporting ligands and is characterized by fast association and very slow dissociation in vitro. The second species of digitalis receptor does not require supporting ligands for ouabain binding and is characterized by slow association and fast dissociation. To determine which species of digitalis receptor is associated with the positive inotropic action of digitalis, ouabain washout experiments were conducted using various isolated canine myocardial preparations. Washout of the positive inotropic effects of 1.2–2.4 × 10−7 M ouabain gave half-life values of 1.5–2.0 h for the various myocardial preparations. [3H]ouabain dissociation from the second species of digitalis receptors gave half-life values of 1.7–1.8 h, whereas dissociation from the sarcolemma Na–K ATPase gave half-life values of 8.9–9.3 h for the various sarcolemma preparations utilized. Therefore, based on similarities in half-life values between ouabain inotropy and [3H]ouabain dissociation from the second class of digitalis receptors, it is postulated that the positive inotropic action of digitalis glycosides is associated with the second species of digitalis receptors in the sarcolemma and not with the digitalis inhibitory receptor of Na–K ATPase for nontoxic concentrations of digitalis.

Sign in / Sign up

Export Citation Format

Share Document